Kadriye Nehir Cosgun, PhD
Research ScientistCards
About
Research
Publications
2025
Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia
Cheng Z, Kume K, Shi R, Robinson M, Cosgun K, Bao Y, Chen S, Mishra P, Bewersdorf J, Xu M, Müschen M. Alternating cycles of quiescent and proliferative cell states determine stemness and leukemia-initiation capacity in acute lymphoblastic leukemia. Blood 2025, 146: 1485-1485. DOI: 10.1182/blood-2025-1485.Peer-Reviewed Original ResearchLeukemia-initiating cellsB-ALL cellsCell state transitionsAcute myeloid leukemiaLeukemia-initiating cell populationProliferative cell statesCell statesB-ALLFusion proteinTime-lapse imagingDry massKnockin alleleClonal hierarchyIntegrated ChIP-seqCatabolic metabolismMultiplex immunofluorescenceGene expression studiesDrug resistanceCellular dry massTime-lapse fluorescence imagingQuiescent cell stateLeukemia-initiating potentialChIP-seqDegron systemProtein synthesis pathwaysTargeted hyperactivation of oncogenic STAT5-signaling in acute lymphoblastic leukemia
Kume K, Cheng Z, Lin J, Xu L, Xiao G, Robinson M, Leveille E, Bramson E, Cosgun K, Geng H, Heinäniemi M, Graeber T, Abkowitz J, Chi H, Alexander W, Chiarle R, Leonard W, Müschen M. Targeted hyperactivation of oncogenic STAT5-signaling in acute lymphoblastic leukemia. Blood 2025, 146: 433-433. DOI: 10.1182/blood-2025-433.Peer-Reviewed Original ResearchLoss-of-functionB-ALL cellsLeukemia-initiating capacityCell statesER stressColony formationLoss of colony formationLeukemia cellsAmino acid metabolic pathwaysActivation of MYCExpression levelsGenetic deletionProliferative cell statesTime-lapse experimentsInhibitors of JAK2Oncogenic tyrosine kinasesActivation of BCL6Autophagosome biogenesisPtdEtn synthesisBCL6 target genesTCA cycleGene setsSTAT5 regulationCell-statesTranscriptional programsTargeting β-catenin nuclear export and protein degradation in high-risk acute lymphoblastic leukemia
Forward J, Cosgun K, Fera E, Bhojwani D, Teachey D, Müschen M. Targeting β-catenin nuclear export and protein degradation in high-risk acute lymphoblastic leukemia. Blood 2025, 146: 3371-3371. DOI: 10.1182/blood-2025-3371.Peer-Reviewed Original ResearchCargo proteinsLeukemia cell deathNuclear exportProtein degradationB-ALL cellsCell deathAcute lymphoblastic leukemia cellsNuclear localizationAcute lymphoblastic leukemiaXPO1 inhibitionT-ALLProtein degradation mechanismsLeukemia cell survivalAdvanced clinical developmentB-cateninGain-of-function mutationsGain-of-functionT-ALL cellsInhibitor of XPO1T-ALL xenograftsWestern blottingCRISPR engineeringCancer cell linesDegradation complexExpression reportersApoptotic rewiring via PI3K hyperactivation as a therapeutic strategy in B-cell malignancies
Martindale S, Leveille E, Wang J, Ito T, Cosgun K, Davids M, Müschen M. Apoptotic rewiring via PI3K hyperactivation as a therapeutic strategy in B-cell malignancies. Blood 2025, 146: 437-437. DOI: 10.1182/blood-2025-437.Peer-Reviewed Original ResearchBCL2 dependencyBcl-xLCell deathMCL cell linesB-cell malignanciesPI3K hyperactivationCell linesCaspase inhibitor Z-VAD-FMKPan-caspase inhibitor Z-VAD-FMKInhibitor Z-VAD-FMKAnti-apoptotic dependencyDynamic BH3 profilingCaspase-dependent mechanismZ-VAD-FMKBCL2 inhibitionCRISPR knockout screenBCL2 inhibitor venetoclaxSynthetic lethal genesNegative selectionAnti-apoptotic protein Bcl2Whole-genome CRISPR knockout screenB-ALLPharmacological inhibitionB cellsCompetitive growth assaysIdentification of NAE1-dependent β-catenin neddylation as selective vulnerability in B-cell malignancies
Cosgun K, Ito T, Robinson M, Fera E, Oulghazi S, Feng Y, Forward J, Yin T, Xin G, Chen S, Davids M, Müschen M. Identification of NAE1-dependent β-catenin neddylation as selective vulnerability in B-cell malignancies. Blood 2025, 146: 5042. DOI: 10.1182/blood-2025-5042.Peer-Reviewed Original ResearchB cell selectionCre-mediated deletionCell deathB-cell malignanciesAcute cell deathProteasomal degradationProtein degradationNedd8-E3 ligaseLoss of colony formationMantle cell lymphomaB-cell tumorsB-ALLCRISPR-KO screensCRISPR-mediated deletionB cellsPre-B cell transitionPro- to pre-B cell transitionNext generation sequencingNEDD8-activating enzymeB-cateninB cell developmentHematopoietic reconstitutionCell lymphomaExpression of MYCLeukemia-initiating abilityTargeting immunoproteasome-dependent β-catenin degradation as a therapeutic strategy in Relapsed/Refractory acute lymphoblastic leukemia
Forward J, Cosgun K, Yin T, Fera E, Bhojwani D, Teachey D, Müschen M. Targeting immunoproteasome-dependent β-catenin degradation as a therapeutic strategy in Relapsed/Refractory acute lymphoblastic leukemia. Blood 2025, 146: 5092-5092. DOI: 10.1182/blood-2025-5092.Peer-Reviewed Original ResearchT-ALL cellsB-ALL cellsProtein degradationTranscriptional activityGenetic deletionCell deathProtein degradation machineryT-ALLCellular stress responsePharmacological inhibitionProtein degradation mechanismsLymphoid leukemia cell linesAcute lymphoblastic leukemiaB-cateninExpression of MYCT-cell acute lymphoblastic leukemiaLeukemia cell linesAcute lymphoblastic leukemia cellsProtein homeostasisDegradation machineryCRISPR engineeringGenetic evidenceCatalytic subunitExpression reportersB-ALLHarnessing repressive LEF1/β-catenin complexes to overcome drug resistance in chronic lymphocytic leukemia
Cosgun K, Ito T, Robinson M, Fera E, Mishra P, Forward J, Iyer P, Wang L, Vaisitti T, Deaglio S, Buchner M, Xue H, Davids M, Müschen M. Harnessing repressive LEF1/β-catenin complexes to overcome drug resistance in chronic lymphocytic leukemia. Blood 2025, 146: 5659-5659. DOI: 10.1182/blood-2025-5659.Peer-Reviewed Original ResearchNuclear translocation of b-cateninCLL cellsB cellsSolid tumorsB-cateninGSK3B inhibitionRichter transformationLEF1 expressionCLL developmentH3K27ac signalPK/PD profilesClinical trialsNuclear translocationB cell-specific deletionMYC enhancer regionChronic lymphocytic leukemiaB-cell leukemiaMyc repressionNormal B cellsCell deathExpression of MYCWnt/b-catenin signalingIntracellular FACSLymphocytic leukemiaMechanism of action
2024
Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies
Robinson M, Li Q, Zhang C, Zhan C, Cheng Z, Kume K, Cosgun K, Kothari S, Agadzhanian N, Nakada D, Müschen M. Identification of Nuclear NAD+ Salvage As a Therapeutic Vulnerability in B-Lymphoid Malignancies. Blood 2024, 144: 4164-4164. DOI: 10.1182/blood-2024-205729.Peer-Reviewed Original ResearchB-ALL cell linesB-ALLB cellsCell linesTherapeutic vulnerabilitiesGene dependenciesNAD+ synthesisMature B-cell lymphomasElimination of B cellsTreatment of B-ALLNAD+ salvageChemotherapy-based regimensEffects of NAMPT inhibitionB-cell depletionB-cell lymphomaB-lymphoid malignanciesB-ALL cellsNAMPT inhibitorsInhibition of NAMPTATP-utilizing enzymesNAD+ salvage pathwayDrug repurposing platformNAD biosynthetic pathwayNear-complete ablationDe novo pathwayIdentification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies
Cosgun K, Robinson M, Agadzhanian N, Cheng Z, Oulghazi S, Berning P, Fonseca-Arce D, Kume K, Fontaine J, Chan L, Lee J, Yu F, Qian Z, Song J, Chan W, Chen J, Taketo M, Schjerven H, Müschen M. Identification of High-Efficiency β-Catenin Protein Degradation As Critical Vulnerability in B-Cell Malignancies. Blood 2024, 144: 4125-4125. DOI: 10.1182/blood-2024-208125.Peer-Reviewed Original ResearchProtein degradation pathwaysB-ALL cellsProtein degradationRepression of MYCTranscriptional activity of MYCCell deathAcute cell deathLoss of colony formationChIP-seq analysisActive enhancer marksB-cell malignanciesSuper-enhancer regionsActivation of MYCIkaros transcription factorB-lymphoid cellsCell linesB cell identityDefective protein degradationB-cateninNon-lymphoid cell linesDegradation pathwayMantle cell lymphomaProtein levelsB-ALLChIP-seqPKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia
Sun R, Lee J, Artadji D, Robinson M, Kume K, Cheng Z, Cosgun K, Chan L, Leveille E, Ma N, Geng H, Paietta E, Vaidehi N, Müschen M. PKCδ-Mediated Phosphorylation of CD25 Initiates Feedback Control of Oncogenic Tyrosine Kinases in Acute Lymphoblastic Leukemia. Blood 2024, 144: 632-632. DOI: 10.1182/blood-2024-211038.Peer-Reviewed Original ResearchB-ALL cellsPatient-derived xenograftsPh+ B-ALLPh-like B-ALLAntibody-drug conjugatesB-ALL casesB-ALLCre-mediated deletionOncogenic tyrosine kinasesBCR-ABL1Tyrosine kinase signalingSurface expressionColony formation capacityCD25 mRNACell surface expression of CD25Tyrosine kinaseGenetic deletionSurface expression of CD25Oncogenic tyrosine kinase signalingKinase signalingOncogene BCR-ABL1Transplant recipient miceControl ADCNegative feedback regulationExpression of CD25
Academic Achievements & Community Involvement
News
News
- December 09, 2025
Yale research advances presented at American Society of Hematology annual meeting
- February 26, 2025
Celebrating Yale Cancer Center Faculty, Research Scientists
- December 18, 2024
Yale research advances presented at American Society of Hematology annual meeting
- October 03, 2024
Yale Department of Internal Medicine Faculty Promotions and Appointments (October 2024)